Urinary tract infections (UTIs) are among the most common infectious diseases contracted by humans. Most UTIs are caused by strains of uropathogenic Escherichia coli (UPEC) that can bind and invade bladder epithelial cells. Within host bladder cells, UPEC can either multiply or enter a non-replicative state that can persist for months in the absence of clinical symptoms and un-phased by host defensive mechanisms and standard antibiotic treatments. It has been proposed that these persistent intracellular bacteria can serve as a reservoir for future recurrent acute infections. Identification of the bacterial genes that control and modify the intracellular lifestyle of UPEC within bladder epithelial cells is the primary goal of this application. We will utilize an arsenal of genetic screens and selection techniques coupled with gene expression profiling and specific gene knockout studies to define UPEC virulence factors that come into play within host bladder cells. This work will provide detailed insight into the genes and mechanisms used by UPEC to persist within host bladder cells, replicate intracellularly and eventually re-emerge.